Variant form of urate oxidase and use thereof

Abstract

The present invention relates to genetically modified proteins with uricolytic activity. More specifically, the invention relates to proteins comprising truncated urate oxidases and methods for producing them, including PEGylated proteins comprising truncated urate oxidases.

We claim: 
     
       1. A method for lowering elevated uric acid levels in a patient comprising administering to said patient an intravenous injection of PEG-uricase having a dosage from about 0.5 to about 24 mg of uricase, the uricase comprising the amino acid sequence of SEQ ID NO: 7, wherein said administration takes place from about every 2 to 4 weeks. 
     
     
       2. The method of  claim 1 , wherein said dosage is between 4 and 8 mg of uricase. 
     
     
       3. The method of  claim 1 , wherein said dosage is between 8 and 12 mg of uricase. 
     
     
       4. The method of  claim 1 , wherein said dosage is about 4 mg of uricase. 
     
     
       5. The method of  claim 1 , wherein said dosage is about 8 mg of uricase. 
     
     
       6. The method of  claim 1 , wherein said dosage is about 12 mg of uricase. 
     
     
       7. The method of  claim 2 , wherein the about 4 mg of uricase is administered every two weeks. 
     
     
       8. The method of  claim 5 , wherein the about 8 mg of uricase is administered every two weeks. 
     
     
       9. The method of  claim 5 , wherein the about 8 mg of uricase is administered every four weeks. 
     
     
       10. The method of  claim 6 , wherein about 12 mg of uricase is administered every four weeks. 
     
     
       11. The method of  claim 1 , wherein the uric acid levels are lowered to 6.8 mg/dL or less. 
     
     
       12. The method of  claim 11 , wherein the uric acid levels are lowered to 6 mg/dL or less. 
     
     
       13. The method of  claim 1 , wherein said patient is suffering from hyperuricemia, gout or hyperuricemia and gout. 
     
     
       14. The method of  claim 1 , wherein said patient has a plasma level of uric acid (PUA) of more than about 6 mg/dL before said administration. 
     
     
       15. A method for lowering elevated uric acid levels in a patient comprising administering to said patient an intravenous injection of PEG-uricase having a dosage from about 4 to about 12 mg of uricase, the uricase consisting of the amino acid sequence of SEQ ID NO: 7, wherein the PEG-uricase administration takes place from about every 2 to 4 weeks. 
     
     
       16. The method of  claim 15 , wherein said dosage is between 4 and 8 mg of uricase. 
     
     
       17. The method of  claim 15 , wherein said dosage is between 8 and 12 mg of uricase. 
     
     
       18. The method of  claim 15 , wherein said dosage is about 4 mg of uricase. 
     
     
       19. The method of  claim 15 , wherein said dosage is about 8 mg of uricase. 
     
     
       20. The method of  claim 15 , wherein said dosage is about 12 mg of uricase. 
     
     
       21. The method of  claim 18 , wherein the about 4 mg of uricase is administered every two weeks. 
     
     
       22. The method of  claim 19 , wherein the about 8 mg of uricase is administered every two weeks. 
     
     
       23. The method of  claim 19 , wherein the about 8 mg of uricase is administered every four weeks. 
     
     
       24. The method of  claim 20 , wherein about 12 mg of uricase is administered every four weeks. 
     
     
       25. The method of  claim 15 , wherein the uric acid levels are lowered to 6.8 mg/dL or less. 
     
     
       26. The method of  claim 25 , wherein the uric acid levels are lowered to 6 mg/dL or less. 
     
     
       27. The method of  claim 15 , wherein said patient is suffering from hyperuricemia, gout or hyperuricemia and gout. 
     
     
       28. The method of  claim 15 , wherein said patient has a plasma level of uric acid (PUA) of more than about 6 mg/dL before said administration.